BACKGROUND: Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of growth factors and affects the survival and plasticity of neurons in the adult central nervous system. The high correlation between cortical and serum BDNF levels has led to many human studies on BDNF levels in various populations, however knowledge about determinants that influence BDNF is lacking. AIMS: To gain insight into the factors that influence BDNF levels in humans. METHODS: In 1168 people aged 18 through 65, free of antidepressants and current psychiatric disease, from the Netherlands study of depression and anxiety four categories of determinants (sampling, sociodemographics, lifestyle indicators and diseases) were measured as well as BDNF level. We used univariate analyses as well as multivariate linear regression analyses in particular to determine which of the possible determinants significantly influenced serum BDNF levels. RESULTS: The mean BDNF level was 8.98ng/ml (SD 3.1ng/ml) with a range from 1.56ng/ml through 18.50ng/ml. Our final multivariate regression analysis revealed that a non-fasting state of blood draw (beta=-.067; p=.019), later measurement (beta=-.065; p=.022), longer sample storage (beta=-.082; p=.004) and being a binge drinker (beta=-.063; p=.035) all resulted in attenuated BDNF levels. This was in contrast to smoking (beta=.098; p=.001) and living in an urban area (beta=.109; p<.001), which resulted in increased BDNF levels. Moreover we found that older subjects also had higher BDNF levels, but this only applied to women (beta=.226; p<.001). CONCLUSIONS: Future studies on serum levels of BDNF in humans should correct for the time of blood withdrawal, storage, urbanicity, age, sex, smoking status and food and alcohol intake.